
Because of Herceptin's (trastuzumab) significant clinical benefits in extending survival for HER2+ metastatic breast cancer patients, it is important to accurately determine the HER2 status of all patients with invasive breast cancer.
IHC detects HER2 overexpression at the protein level, and may be affected by conditions of the testing procedures. These include: time to fixation, duration of fixation, processing, denaturation, heating, antigen retrieval, the staining procedure used, and the interpretation of staining.3,7 Although there are antigen retrieval techniques in use, these may result in false-positive IHC results. FISH measures HER2 DNA. Some fixatives, chemicals or heat, may interfere with the FISH assay. However, an internal control is used to distinguish between a FISH-negative and a non-informative result.6 Scoring difficulties associated with FISH testing may be caused by difficulties in identifying specific invasive cells to include in the determination.
HER2 testing should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance may result from the use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation and can lead to unreliable results. 1,8
Recent findings suggest the need to improve quality control measures in laboratories that use IHC assays, including periodic testing for concordance with FISH. These studies also suggest that large-volume reference laboratories performing HER2 tests are more reliable than small-volume laboratories.3,9 HER2 testing should be done in laboratories accredited to perform such testing. Ongoing proficiency testing is a necessary component of a laboratory's qualification for accreditation.
Rate of discordance* between initial test from local lab and subsequent central lab test was assessed in Herceptin adjuvant trial NSABP B-31
*Discordance defined as differing HER2 test result between initial local testing and follow-up central testing as part of quality assurance protocol. Central lab tested IHC by HercepTest and FISH by PathVysion.
Rates of discordance were lower for labs with greater experience performing the test*
*Discordance defined as differing HER2 test result between initial local testing and follow-up central testing as part of quality assurance protocol. Central lab tested IHC by HercepTest and FISH by PathVysion.
Labs are required to demonstrate proficiency in specific assays to maintain CAP accreditation 4,5
Collaboration among specialists-including pathologists, surgeons, radiologists, and oncologists-is critical to help ensure accurate interpretation of results and appropriate disease management
Herceptin can cause oligohydramnios and fetal harm when administered to a pregnant woman.
The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.
Please see the Herceptin full prescribing information including Boxed WARNINGS and additional important safety information.
